Neural mechanisms underlying the development of anxiety and risk taking in adolescence

Anxiety is one of the most common disorders affecting children and adolescents worldwide. The average age of onset for clinical anxiety is in adolescence, a key period of brain and behavioral development that marks the transition from childhood to adult independence. Despite these overlapping developmental timelines, phenotypic anxiety is often characterized by persistent avoidant behavior which conflicts with normative hallmarks of adolescence such as risk taking and exploration. While research suggests that shared neural mechanisms contribute to both the rise of anxiety and risk taking in adolescence, the field has primarily studied these two topics in isolation, precluding the opportunity to understand how brain development contributes to both phenotypes during this period and identify factors that promote healthy development across decision-making and mental health domains. The studies presented in this dissertation aim to fill this gap in the literature by examining the concurrent development of anxiety symptoms and risky decision-making behaviors in a diverse sample of children and adolescents living in the greater Los Angeles Area over two timepoints separated by 1-3 years. At each timepoint, participants completed a clinical interview and an fMRI scan while performing tasks aimed at measuring risky decision-making and cognitive control. Results from Study 1 suggest that anxious adolescents engage in a similar degree of risky behavior as their peers but report negative perceptions of their own decision-making and struggle with making decisions in the face of approach-avoidance conflict. Anxious adolescents also demonstrated altered associations between fronto-striatal circuitry and risky behavior such that reduced prefrontal regulation and heightened striatal connectivity was associated with risk avoidance in high anxiety, while these same neural markers were associated with risk taking in low anxiety. Study 2 investigated how approach motivations and anxiety interact to influence adolescent risky decision-making and neural functioning, revealing that the association between anxiety and risk taking is dependent on adolescent approach motivations: anxious adolescents with low approach motivations were risk averse and inhibited, while anxious adolescents with high approach motivations were risk taking and impulsive. Approach motivations and anxiety showed opposing associations with communication between the striatum, amygdala, and prefrontal cortex during risky decision-making and in the resting adolescent brain, highlighting the competing influences of both anxiety and approach motivations on brain and behavioral correlates of risk taking in adolescence. Whole-brain striatal connectivity patterns during risk taking and risk avoidance showed a high degree of overlap in adolescents with low anxiety but showed divergence in adolescents with high anxiety, again suggesting that the sensitized adolescent striatum plays an important role in anxiety and avoidance. In Study 3, longitudinal analyses revealed average group increases in risk taking and decreases in self-reported anxiety symptoms as participants progressed through adolescence, although clinician-rated anxiety scores increased over time. Adolescents who increased in anxiety reported decreases in positive perceptions and increases in negative perceptions of their decision-making over time. Neural response during risk avoidance was linked to the development of both anxiety and risk taking such that increases in anxiety were reflected in increases in striatal connectivity during risk avoidance, while changes in risk taking were reflected in changes in amygdala connectivity during risk avoidance. Increases in anxiety were associated with increased neural generalization across risk avoidance and response inhibition and decreased conflict processing during risk avoidance, while increases in risky behavior were associated with increased neural generalization across risk avoidance and risk taking and heightened conflict processing during risk avoidance. Finally, amygdala and striatal response during risk avoidance interacted to predict the emergence of clinician-rated anxiety over time. Taken together, results from this dissertation help to delineate the shared behavioral and neural mechanisms that contribute to anxiety and risky decision-making in adolescents and highlight the potential of leveraging these shared mechanisms to promote positive approaches to decision-making amongst developing youth